Purpose Corneal epithelial homeostasis is maintained by coordinated gene expression across distinct cell populations, but the gene regulatory programs underlying this cellular diversity remain to be characterized. Here we applied single-cell multi-omics analysis to delineate the gene regulatory profile of mouse corneal epithelial cells under normal homeostasis. Methods Single cells isolated from the cornea epithelium (with marginal conjunctiva) of adult mice were subjected to scRNA-seq and scATAC-seq using the 10×Genomics platform. Cell types were clustered by the graph-based visualization method uniform manifold approximation and projection and unbiased computational informatics analysis. The scRNA-seq and scATAC-seq datasets were integrated following the integration pipeline described in ArchR and Seurat. Results We characterized diverse corneal epithelial cell types based on gene expression signatures and chromatin accessibility. We found that cell type–specific accessibility regions were mainly located at distal regions, suggesting essential roles of distal regulatory elements in determining corneal epithelial cell diversity. Trajectory analyses revealed a continuum of cell state transition and higher coordination between transcription factor (TF) motif accessibility and gene expression during corneal epithelial cell differentiation. By integrating transcriptomic and chromatin accessibility analysis, we identified cell type-specific and shared gene regulation programs. We also uncovered critical TFs driving corneal epithelial cell differentiation, such as nuclear factor I (NFI) family members, Rarg, Elf3. We found that nuclear factor-κB (NF-κB) family members were positive TFs in limbal cells and some superficial cells, but they were involved in regulating distinct biological processes. Conclusions Our study presents a comprehensive gene regulatory landscape of mouse cornea epithelial cells, and provides valuable foundations for future investigation of corneal epithelial homeostasis in the context of cornea pathologies and regenerative medicine.

Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Mouse Corneal Epithelial Cells

Prioritization of genes associated with type 2 diabetes mellitus for functional studies

Obesity has become one of the most urgent public health problems globally with the steepest increases in prevalence reported among socioeconomically disadvantaged groups. In resource-rich settings, many of these disadvantaged are also ethnic minorities. In adults, obesity is associated with sizable reductions in life expectancy and quality of life, but it also is a consistent risk factor for comorbid conditions that include type 2 diabetes, cardiovascular diseases, and multiple forms of cancer and is fueling the increase in chronic liver diseases. In children, obesity is associated with school absenteeism and lower educational attainment, and as adults, lower income and occupational productivity, and thus a higher likelihood of poverty. Although animal and in vitro evidence supports that epigenetic dysregulation may be causally related to obesity, the affected pathways remain obscure. This chapter summarizes obesity-related human data on CpG methylation of DNA, the most studied epigenetic mechanism in humans, in the context of causal inference. Particular focus is given to epigenetic marks established before tissue-specification, including those regulating genomically imprinted genes, as well as metastable epialleles, and the identification of these regions in adults and children using methods made possible by recent advances in technologies for genome-scale methylation microarrays and methyl-sequencing. Still limited, however, are data on the temporal stability of regions identified thus far, and data on obesity-related sequence regions in populations including the socioeconomically disadvantaged and ethnic minorities. To enhance causal inference, we therefore conclude with a call for studies that evaluate these issues, examining the temporal stability and association with socioeconomic and ethnic differences for obesity-associated DNA methylation marks identified thus far. 

Epigenomics and human obesity

Background/Objectives: Skin hyperpigmentation is a biological process that results in an excessive production of melanin and is highly regulated by several mechanisms, tyrosinase being one of the key enzymes involved. Current reported inhibitors lack clinical efficacy, show toxic side effects, have poor bioavailability, or low formulation compatibility. The aim of this study was to design a new effective tyrosinase inhibitor for topical hyperpigmentation and anti-aging treatments. Methods: Homology modeling was used to build the tridimensional structure of human tyrosinase, and virtual docking was used to predict molecule–enzyme binding modes. The tyrosinase activity of the designed and synthesized compounds was assessed and water solubility was determined by HPLC. Cell assays were performed to determine melanin content, cytotoxicity, wound healing, anti-glycation, antioxidation, and autophagy efficacy. Gene expression and miRNA levels were quantified by qPCR and chromatin accessibility by ATAC-Seq. Human reconstructed epidermis was used to test the depigmenting efficacy as well as the skin irritation potential. Results: The 3D structure of human tyrosinase was designed and validated. The new molecule could effectively inhibit human tyrosinase and melanin synthesis in 2D monocultures and a 3D epidermis model. Two melanogenesis-related miRNAs were increased in treated cells. Anti-glycation, antioxidant, mitochondria protection, autophagy activation, and wound healing properties were also observed, with special emphasis on epigenetics. Conclusions: The designed molecule is a potential candidate to be used as a depigmenting and anti-aging agent, with suitable properties to be introduced in final product formulations for dermatology or cosmetics treatments. 

New Chalcone-Derived Molecule for the Topical Regulation of Hyperpigmentation and Skin Aging

Although significant advancement has been made in the study of adipogenesis, knowledge about how chromatin accessibility regulates yak adipogenesis is lacking. We here described genome-wide dynamic chromatin accessibility in preadipocytes and adipocytes by using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), and thus revealed the unique characteristics of open chromatin during yak adipocyte differentiation. The chromatin accessibility of preadipocytes and adipocytes exhibited a similar genomic distribution, displaying a preferential location within the intergenic region, intron, and promoter. The pathway enrichment analysis identified that genes with differential chromatin accessibility were involved in adipogenic metabolism regulation pathways, such as the peroxisome proliferator activated receptor-γ (PPAR) signaling pathway, wingless-type MMTV integration site (Wnt) signaling pathway, and extracellular matrix-receptor (ECM–receptor) interaction. Integration of ATAC-seq and mRNA-seq revealed that genes with a high expression were associated with high levels of chromatin accessibility, especially within 1 kb upstream and downstream of the transcription start site. In addition, we identified a series of transcription factors (TFs) related to adipogenesis and created the TF regulatory network, providing the possible interactions between TFs during yak adipogenesis. This study is crucial for advancing the understanding of transcriptional regulatory mechanisms of adipogenesis and provides valuable information for understanding the adaptation of plateau species to high-altitude environments by maintaining whole body homeostasis through fat metabolism.

https://www.mdpi.com/1422-0067/23/17/9960/pdf?version=1662038717

The Landscape of Accessible Chromatin during Yak Adipocyte Differentiation

ABSTRACT Obesity has become a serious global public health problem; a deeper understanding of systemic change of chromatin accessibility during human adipogenesis contributes to conquering obesity and its related diseases. Here, we applied the ATAC-seq method to depict a high-quality genome‐wide time-resolved accessible chromatin atlas during adipogenesis of human adipose-derived stem cells (hASCs). Our data indicated that the chromatin accessibility drastic dynamically reformed during the adipogenesis of hASCs and 8 h may be the critical transition node of adipogenesis chromatin states from commitment phase to determination phase. Moreover, upon adipogenesis, we also found that the chromatin accessibility of regions related to anti-apoptotic, angiogenic and immunoregulatory gradually increased, which is beneficial to maintaining the health of adipose tissue (AT). Finally, the chromatin accessibility changed significantly in intronic regions of peroxisome proliferator‐activated receptor γ during adipogenesis, and these regions were rich in transcription factors binding motifs that were exposed for further regulation. Overall, we systematically analysed the complex change of chromatin accessibility occurring in the early stage of adipogenesis and deepened our understanding of human adipogenesis. Furthermore, we also provided a good reference data resource of genome‐wide chromatin accessibility for future studies on human adipogenesis.

https://www.tandfonline.com/doi/pdf/10.1080/21623945.2022.2063015?needAccess=true

A chromatin accessibility landscape during early adipogenesis of human adipose-derived stem cells

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Xiaolin Zong

Author Tools

Chat about Author

Papers

A chromatin accessibility landscape during early adipogenesis of human adipose-derived stem cells